Zhao Xiaoling, Ding Jie, Jin Danqun
Department of Intensive Care Unit, Anhui Provincial Children's Hospital, Hefei, Anhui 230051, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2022 Sep 10;39(9):996-1000. doi: 10.3760/cma.j.cn511374-20210719-00606.
To analyze the clinical features and genetic basis for a child with pyruvate carboxylase deficiency type A (PCD-A).
Clinical data of the child was retrospectively analyzed. The child and his parents were subjected to trio-whole exome sequencing, and candidate variants were verified by bioinformatics analysis.
The child was admitted due to fever with vomiting and disturbance of consciousness. His clinical manifestations included severe decompensated acidosis, hypotension and intractable shock. Cranial MRI showed abnormal signal in the brain, and chest X-ray revealed acute pulmonary edema. DNA sequencing revealed that he has harbored compound heterozygous variants of the PC gene, namely c.182T>C (p.I61T) and c.2581G>A (p.V861M), which were respectively inherited from his father and mother. Neither variant was retrievable in the ClinVar and HGMD databases. Through prediction of protein structure, both variants may affect the functional stability of the protein product.
The compound heterozygous variants of the PC gene probably underlay the PCD-A in this child. Combined with the clinical features, the child was ultimately diagnosed as PCD-A. Above finding has enriched the spectrum of PC gene variation underlying PCD-A.
分析1例A型丙酮酸羧化酶缺乏症（PCD-A）患儿的临床特征及遗传基础。
对该患儿的临床资料进行回顾性分析。对患儿及其父母进行三联体全外显子测序，并通过生物信息学分析验证候选变异。
患儿因发热伴呕吐、意识障碍入院。其临床表现包括严重失代偿性酸中毒、低血压及顽固性休克。头颅磁共振成像显示脑内信号异常，胸部X线显示急性肺水肿。DNA测序显示，他携带PC基因的复合杂合变异，即c.182T>C（p.I61T）和c.2581G>A（p.V861M），分别遗传自其父亲和母亲。这两个变异在ClinVar和HGMD数据库中均未检索到。通过蛋白质结构预测，这两个变异可能影响蛋白质产物的功能稳定性。
PC基因的复合杂合变异可能是该患儿PCD-A的病因。结合临床特征，该患儿最终被诊断为PCD-A。上述发现丰富了PCD-A相关PC基因变异谱。
